BACKGROUND: Increased lung cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately and by multiple quantitative bias analyses, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased the direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung cancer risk in the multiple bias analysis. Lung cancer risks remained increased for lower SES groups, with higher risks in men (fourth vs. first [highest] SES quartile: CDE, 1.50 [SI, 1.32, 1.69]) than women (CDE: 1.20 [SI: 1.01, 1.45]). Natural direct effects were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.

• MeSH
• analýza mediace * MeSH
• dospělí MeSH
• kouření * epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• nádory plic * epidemiologie   MeSH
• odds ratio MeSH
• rizikové faktory MeSH
• senioři MeSH
• společenská třída * MeSH
• studie případů a kontrol MeSH
• zkreslení výsledků (epidemiologie) * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established. METHODS: We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach. FINDINGS: We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes). INTERPRETATION: The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.

• Klíčová slova
• Cardiac arrest, Critical care, Emergency medicine, Extracorporeal cardiopulmonary resuscitation, Extracorporeal life support,
• MeSH
• dospělí MeSH
• kardiopulmonální resuscitace * MeSH
• lidé MeSH
• mimotělní membránová oxygenace * MeSH
• odds ratio MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• zástava srdce mimo nemocnici * terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

BACKGROUND: Evaluating the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH) who may be at risk of poor outcomes using grading systems is one way to make a better decision on treatment for these patients. This study aimed to compare the accuracy of the modified World Federation of Neurosurgical Societies (WFNS), WFNS, and Hunt and Hess (H&H) Grading Scales in predicting the outcomes of patients with aSAH. METHODS: From August 2019 to June 2021, we conducted a multicenter prospective cohort study on adult patients with aSAH in three central hospitals in Hanoi, Vietnam. The primary outcome was the 90-day poor outcome, measured by a score of 4 (moderately severe disability) to 6 (death) on the modified Rankin Scale (mRS). We calculated the areas under the receiver operator characteristic (ROC) curve (AUROCs) to determine how well the grading scales could predict patient prognosis upon admission. We also used ROC curve analysis to find the best cut-off value for each scale. We compared AUROCs using Z-statistics and compared 90-day mean mRS scores among intergrades using the pairwise multiple-comparison test. Finally, we used logistic regression to identify factors associated with the 90-day poor outcome. RESULTS: Of 415 patients, 32% had a 90-day poor outcome. The modified WFNS (AUROC: 0.839 [95% confidence interval, CI: 0.795-0.883]; cut-off value≥2.50; PAUROC<0.001), WFNS (AUROC: 0.837 [95% CI: 0.793-0.881]; cut-off value≥3.5; PAUROC<0.001), and H&H scales (AUROC: 0.836 [95% CI: 0.791-0.881]; cut-off value≥3.5; PAUROC<0.001) were all good at predicting patient prognosis on day 90th after ictus. However, there were no significant differences between the AUROCs of these scales. Only grades IV and V of the modified WFNS (3.75 [standard deviation, SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), WFNS (3.75 [SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), and H&H scales (2.96 [SD: 2.60] vs 4.97 [SD: 1.87], p<0.001, respectively) showed a significant difference in the 90-day mean mRS scores. In multivariable models, with the same set of confounding variables, the modified WFNS grade of III to V (adjusted odds ratio, AOR: 9.090; 95% CI: 3.494-23.648; P<0.001) was more strongly associated with the increased risk of the 90-day poor outcome compared to the WFNS grade of IV to V (AOR: 6.383; 95% CI: 2.661-15.310; P<0.001) or the H&H grade of IV to V (AOR: 6.146; 95% CI: 2.584-14.620; P<0.001). CONCLUSIONS: In this study, the modified WFNS, WFNS, and H&H scales all had good discriminatory abilities for the prognosis of patients with aSAH. Because of the better effect size in predicting poor outcomes, the modified WFNS scale seems preferable to the WFNS and H&H scales.

• MeSH
• dospělí MeSH
• hospitalizace MeSH
• lidé MeSH
• nemocnice MeSH
• odds ratio MeSH
• prospektivní studie MeSH
• subarachnoidální krvácení * diagnóza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND AND AIM: Polypharmacy (concomitant use of 5-9 medicines) and hyperpolypharmacy (concomitant use of over 10 medicines) were observed to be more frequent in older adults (≥65 years) and associated with adverse outcomes. Their prevalence and risk in older patients with Parkinson's disease (PD) remain unknown. We aimed to synthesize the extant evidence on the prevalence and risk of polypharmacy and hyperpolypharmacy in older adults with PD. METHODS: A systematic literature search was performed in PubMed/MEDLINE, Scopus, and Embase databases to identify pertinent studies published from 2000 to July 2021. Observational studies reporting the prevalence and association with disease of polypharmacy/hyperpolypharmacy in older adults with PD were meta-analyzed. Pooled prevalence and odds ratio (OR) with 95% confidence intervals (CIs) were calculated. RESULTS: Out of the total 499 studies identified, 6 fulfilled the inclusion criteria and comprised 7,171 participants. The overall prevalence of polypharmacy and hyperpolypharmacy was 40% (95% CI: 37-44) and 18% (95% CI: 13-23), respectively. A meta-analysis of 4 studies indicated a significant association between polypharmacy (OR: 1.94, 95% CI: 1.26-2.62; p < 0.001) and PD. Hyperpolypharmacy was also strongly associated with PD (OR: 3.11, 95% CI: 2.08-4.14; p < 0.001). CONCLUSION: Polypharmacy (40%) and hyperpolypharmacy (18%) are highly prevalent and eventually increase the risk of drug-related problems in older adults with PD. Therefore, interventions that ensure rational geriatric pharmacotherapy are of critical importance for the older population with neurogenerative disorders.

• Klíčová slova
• Cognitive function, Hyperpolypharmacy, Meta-analysis, Parkinson’s disease, Polypharmacy,
• MeSH
• lidé MeSH
• odds ratio MeSH
• Parkinsonova nemoc * farmakoterapie   epidemiologie   MeSH
• polypharmacy * MeSH
• prevalence MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH

OBJECTIVE: To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America. METHODS: Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs. RESULTS: Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15-60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR <15 ml/min/1.73 m2, OR 6.71 (95% CI: 2.94, 15.33)] involvement were independent variables associated with a higher occurrence of VTE. CONCLUSION: Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE.

• Klíčová slova
• ANCA-associated vasculitis, risk factors, venous thromboembolic events,
• MeSH
• ANCA-asociované vaskulitidy komplikace   imunologie   MeSH
• kožní nemoci epidemiologie   imunologie   MeSH
• kůže imunologie   MeSH
• ledviny imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci ledvin epidemiologie   imunologie   MeSH
• odds ratio MeSH
• plíce imunologie   MeSH
• plicní nemoci epidemiologie   imunologie   MeSH
• regresní analýza MeSH
• retrospektivní studie MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• senioři MeSH
• žilní tromboembolie epidemiologie   imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Severní Amerika epidemiologie   MeSH

PURPOSE: To investigate the prognostic role of the preoperative systemic immune-inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS). RESULTS: Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis. CONCLUSIONS: Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.

• Klíčová slova
• Nephroureterectomy, Systemic immune–inflammation index, Upper tract urothelial carcinoma,
• MeSH
• biologické markery * MeSH
• imunita * MeSH
• lidé MeSH
• odds ratio MeSH
• počet leukocytů MeSH
• počet lymfocytů MeSH
• počet trombocytů MeSH
• prognóza MeSH
• recidiva MeSH
• urologické nádory diagnóza   etiologie   mortalita   terapie   MeSH
• zánět etiologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery * MeSH

OBJECTIVES: To examine the effect of premorbid β-blocker exposure on mortality and organ dysfunction in sepsis. DESIGN: Retrospective observational study. SETTING: ICUs in Australia, the Czech Republic, and the United States. PATIENTS: Total of 4,086 critical care patients above 18 years old with sepsis between January 2014 and December 2018. INTERVENTION: Premorbid beta-blocker exposure. MEASUREMENTS AND MAIN RESULTS: One thousand five hundred fifty-six patients (38%) with premorbid β-blocker exposure were identified. Overall ICU mortality rate was 15.1%. In adjusted models, premorbid β-blocker exposure was associated with decreased ICU (adjusted odds ratio, 0.80; 95% CI, 0.66-0.97; p = 0.025) and hospital (adjusted odds ratio, 0.83; 95% CI, 0.71-0.99; p = 0.033) mortality. The risk reduction in ICU mortality of 16% was significant (hazard ratio, 0.84, 95% CI, 0.71-0.99; p = 0.037). In particular, exposure to noncardioselective β-blocker before septic episode was associated with decreased mortality. Sequential Organ Failure Assessment score analysis showed that premorbid β-blocker exposure had potential benefits in reducing respiratory and neurologic dysfunction. CONCLUSIONS: This study suggests that β-blocker exposure prior to sepsis, especially to noncardioselective β blockers, may be associated with better outcome. The findings suggest prospective evaluation of β-blocker use in the management of sepsis.

• MeSH
• APACHE MeSH
• beta blokátory škodlivé účinky   farmakologie   MeSH
• dospělí MeSH
• hodnocení výsledků zdravotní péče metody   statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• odds ratio MeSH
• proporcionální rizikové modely MeSH
• retrospektivní studie MeSH
• senioři MeSH
• sepse farmakoterapie   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Nový Jižní Wales MeSH
• Spojené státy americké MeSH
• Názvy látek
• beta blokátory MeSH

IMPORTANCE: Chemotherapy during the first trimester of pregnancy should be avoided owing to the risk of congenital malformations. However, the precise gestational age at which chemotherapy can be initiated safely remains unclear. OBJECTIVE: To assess congenital malformation rates associated with gestational age at initiation of chemotherapy among pregnant women with cancer. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study evaluated all pregnant women who received chemotherapy between 1977 and 2019 registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. Data were analyzed from February 15 to June 2, 2020. EXPOSURES: Cancer treatment with chemotherapy during pregnancy. MAIN OUTCOMES AND MEASURES: Analysis was focused on major and minor structural malformations in offspring, defined by EUROCAT, detected during pregnancy or at birth. RESULTS: A total of 755 women in the INCIP database who underwent cancer treatment with chemotherapy during pregnancy were included in analysis. The median (range) age at cancer diagnosis was 33 (14-48) years. Among offspring, the major congenital malformation rate was 3.6% (95% CI, 2.4%-5.2%), and the minor congenital malformation rate was 1.9% (95% CI, 1.0%-3.1%). Chemotherapy exposure prior to 12 weeks gestational age was associated with a high rate of major congenital malformations, at 21.7% (95% CI, 7.5%-43.7%; odds ratio, 9.24 [95% CI, 3.13-27.30]). When chemotherapy was initiated after gestational age 12 weeks, the frequency of major congenital malformations was 3.0% (95% CI, 1.9%-4.6%), which was similar to the expected rates in the general population. Minor malformations were comparable when exposure occurred before or after gestational age 12 weeks (4.3% [95% CI, 0.1%-21.9%] vs 1.8% [95% CI, 1.0-3.0]; odds ratio, 3.13 [95% CI, 0.39-25.28]). Of 29 women who received chemotherapy prior to 12 weeks gestation, 17 (58.6%) were not aware of pregnancy, and 6 (20.7%) experienced a miscarriage (3 women [10.3%]) or decided to terminate their pregnancy (3 women [10.3%]). CONCLUSIONS AND RELEVANCE: This cohort study found that chemotherapy was associated with an increased risk of major congenital malformations only in the first 12 weeks of pregnancy. The risk of congenital malformations when chemotherapy was administered during the first trimester and the high number of incidental pregnancies during cancer treatment in the INCIP registry underscore the importance of contraceptive advice and pregnancy testing at the start of chemotherapeutic treatment in young women with cancer.

• MeSH
• abnormality vyvolané léky etiologie   MeSH
• antitumorózní látky škodlivé účinky   terapeutické užití   MeSH
• časové faktory MeSH
• dospělí MeSH
• gestační stáří MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory farmakoterapie   MeSH
• odds ratio MeSH
• první trimestr těhotenství MeSH
• rozvrh dávkování léků * MeSH
• těhotenství MeSH
• těhotné ženy MeSH
• vývoj plodu účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH

BACKGROUND: Prenatal origins of wheezing are not fully understood. This study develops a model of mechanisms linking perinatal stress exposure to wheeze phenotypes in children. METHODS: Data were obtained from 1880 mother-child dyads participating in ELSPAC-CZ birth cohort. Wheeze phenotypes assessed between birth and age 7 years included "never wheeze," "early-onset transient (EOT) wheeze," "early-onset persistent (EOP) wheeze," and "late-onset (LO) wheeze." Prenatal and postnatal stress exposures were assessed in mid-pregnancy and 6 months after delivery, respectively, using an inventory of 42 life events. RESULTS: In adjusted models, children in the highest tercile (high) versus lowest tercile (low) for prenatal life events had a 38% higher risk of EOT wheeze (relative risk ratio [RRR] = 1.38; 95% confidence interval [CI] = 1.01-1.88; p = .041) and 50% higher risk of LO wheeze (RRR = 1.50; 95% CI = 1.00-2.25; p = .047). High versus low exposure to postnatal life events predicted a 60% increase in relative risk of EOT wheeze (RRR = 1.60; 95% CI = 1.17-2.19; p = .003) and medium versus low exposure was related to an 85% increase in relative risk of EOP wheeze (RRR = 1.85; 95% CI = 1.16-2.95; p = .010). Lower respiratory tract infections and postpartum depression partially mediated between postnatal life events and any wheeze (indirect effects 1.06, 95% CI = 1.02-1.09, p = .003 and odds ratio [OR] = 1.08, 95% CI = 1.02-1.15, p = .012, respectively), while postnatal events mediate for prenatal events (indirect effect OR = 1.11; 95% CI = 1.03-1.18; p = .005). CONCLUSIONS: Exposures to prenatal and postnatal life events are risk factors for the development of wheezing. Prenatal stress contributes to wheeze directly and also through postnatal life events, respiratory infections, and maternal depression.

• Klíčová slova
• child wheezing, early life stress, maternal depression, respiratory infections,
• MeSH
• dítě MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• odds ratio MeSH
• respirační zvuky * etiologie   MeSH
• rizikové faktory MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * epidemiologie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 × 10-9) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R2 = 0.15; P < 2.0 × 10-22 at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.

• Klíčová slova
• GWAS, Kleine-Levin syndrome, bipolar disorder, birth difficulties, hypersomnia,
• MeSH
• bipolární porucha etiologie   MeSH
• cytokiny genetika   MeSH
• genetická predispozice k nemoci MeSH
• genetická variace * MeSH
• genetické asociační studie MeSH
• hodnocení rizik MeSH
• Kleineho-Levinův syndrom komplikace   epidemiologie   genetika   MeSH
• komplikace porodu epidemiologie   etiologie   MeSH
• lidé MeSH
• náchylnost k nemoci * MeSH
• odds ratio MeSH
• polymorfismus genetický MeSH
• poruchy nadměrné spavosti etiologie   MeSH
• rizikové faktory MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• cytokiny MeSH
• TRANK1 protein, human MeSH Prohlížeč